Binding conformation

The time window available for FRET is dictated by the lifetime of the donor. Is there an optimal lifetime If very short , it is more difficult to measure in FLIM. If it is very long , the levels of fluorescence are low ( /-limited , [1]). In addition, the lifetime is a relevant parameter when one is interested in dynamics, either of binding, conformational change, or diffusion (translational, rotational). These processes influence FRET via the parameters K2 andrDA (Table 12.1). Long lifetimes are useful in luminescence RET (LRET) and can help to reduce background and increase signal-to-noise ratios. 

The structural information from the simulations also readily explained the experimentally observed binding trends. Furthermore, the docking and FEP results have provided clarification of the binding conformation of the phenylsulfonamide moiety, which is, in fact, rotated nearly 180° from what was originally reported in the 1CX2 crystal structure. 

Frimurer TM, Peters GH, Iversen LF, Andersen HS, Moller NP, et al. 2003. Ligand-induced conformational changes improved predictions of ligand binding conformations and affinities. Biophys J 84(4) 2273-2281. 

The spectra from the NDO-naphthalene complex also revealed a second binding conformation (denoted as B), in which the substrate is located -0.5 A from the Fe atom. (From Yang et ah, 2003)... 

There are various methods to conduct a fragment screening campaign. The most commonly utilized methods include various NMR techniques, mass spectrometry, SPR, and biochemical screens. X-ray crystallization is a preferred method since it provides a binding conformation, but can only be used when the target protein is well behaved. Various calorimetry techniques have also been used for fragment screening, but these have been less commonly utilized. The merits of each method have been discussed in the literature (26) and will not be outlined here. 

They reasoned that if HIV PR incorporates symmetry into its active site structure, compounds that mimic this symmetry might be novel, more specific, and potent inhibitors and, furthermore, due to the bidirectionality of peptide bonds, might be sufficiently less peptidic in character and pharmacologically superior to the classical peptide-based compounds. The crystal structure of one of the first compounds from this series (A74704) verified the assumption of symmetrical binding conformation in the... 

Either directly (2) or indirectly (1 or 3) peptides will be selected as ligands having affinity for the receptor. The biologically active (receptor binding) conformation of the peptide must now be determined through X-ray, NMR or computational methods. Finally, it is desirable that a non-peptide surrogate be designed. 

---